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Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
James Graham Brown Cancer Centre.
James Graham Brown Cancer Centre.
University of Louisville.
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2010 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 49, no 3, 401-407 p.Article in journal (Refereed) Published
Abstract [en]

In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4 weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. OCR amplification of near-full-length (similar to 16 kb) mtDNA revealed greater than50% loss of full-length product, whereas amounts of a OCR product of a nuclear gene (13 kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60-70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 49, no 3, 401-407 p.
Keyword [en]
Mitochondrial DNA; Iron overload; Cardiomyopathy
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-58233DOI: 10.1016/j.freeradbiomed.2010.04.033ISI: 000279645700011OAI: diva2:338040
Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2010-08-10

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Gao, XueshanSun, Xiao-Feng
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Oncology Faculty of Health SciencesDepartment of Oncology UHL
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